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Journal Article
Research Support, Non-U.S. Gov't
A novel lactoferrin-modified β-cyclodextrin nanocarrier for brain-targeting drug delivery.
International Journal of Pharmaceutics 2013 December 16
The blood-brain barrier (BBB) restricts the transfer and delivery of most drug substances to brain. In this study, a novel nano-drug delivery system for brain-targeting was developed and investigated in vitro and in vivo. Lactoferrin (Lf) was selected as a brain-targeting ligand and conjugated to β-cyclodextrin (β-CD) via the heterobifunctional polyethyleneglycol (PEG) linker NHS-PEG-MAL, yielding Lf conjugated β-cyclodextrin (Lf-CD). UV-vis, FTIR, NMR and transmission electron microscopy (TEM) techniques clearly demonstrated the successful synthesis of Lf-CD nanoparticles with the average diameter of 92.9 ± 16.5 nm. Using near-infrared fluorescent dye IR-775 chloride (IR) as a model compound of poorly water-soluble drugs, IR-loaded Lf-CD nanoparticles (Lf-CD/IR) were successfully prepared with a high entrapment efficiency of 98.1 ± 4.8%. Biodistribution and pharmacokinetics of Lf-CD/IR were evaluated in KM mice after intravenous administration. The results of tissue distribution studies revealed that Lf-CD/IR treatment showed greatly improved BBB transport efficiency. In addition, AUC0-2h of IR in brain after Lf-CD/IR treatment was seven fold higher compared with that of IR treatment without Lf-CD nano-carriers, demonstrating that the introduction of Lf-CD drug-delivery system positively resulted in a higher AUC located in brain tissue. These results provide evidence that Lf-CD nanoparticles could be exploited as a potential brain-targeting drug delivery system for hydrophobic drugs and diagnostic reagents which normally fail to pass through the BBB.
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